Cholecystokinin (CCK) is a peptide common to gut and brain. It is very abundant in brain and displays many neurotransmitter actions. CCK is abundant in the striatum and because of its anti-tremor activity, it has been suggested that CCK may play a role in regulation of extrapyramidal motor activity. Observed decreases in CCK levels in brain and CSF in Parkinson's patients and in brain in Huntington's patients suggest alteration in CCK function in these neurological diseases. The long term objective of this research is to understand the role of CCK in the striatum. Investigating the regulation of CCK release in the striatum may lead to insight into how transmitter inbalance in Huntington's and Parkinson's disease may influence striatal neurons and how this may be reversed pharmacologically. Studies on the biosynthesis of CCK in the hippocampal slice will provide more information about how CCk is made and what factors might modify this. This information may lead to better therapeutic regulation of the symptoms of Parkinsons disease. The specific aims of the proposal are: Aim 1: To continue studies on the regulation of CCK release from the rat cp focusing on the identity of the unknown inhibitory factor "X" and on the possible role of known neuroactive substances in the cp as this factor. Aim 2: To examine in detail the distribution in brain and the mechanism of action of the lithium-stimulation of CCK release from rat cp. Aim 3: To study the steps in the biosynthesis and processing of CCK using the rat hippocampal slice preparation and determine the rate of turnover of CCK in this preparation in vitro. Aim 4: To examine the influence of factors known to alter synthesis and release of other neuropeptides (enhanced release, cyclic nucleotides, ascorbic acid and agents which activate protein kinase C) on CCK synthesis and turnover.